DESCRIPTION (Applicant's Description): Retinitis pigmentosa (RP) is a group of inherited retinal degenerative diseases causing blindness. Currently there are no cures for these disorders. The visual deficits are due to progressive apoptotic cell death of retinal photoreceptors. Intravitreal injections of survival-promoting proteins, including ciliary neurotrophic factor (CNTF), have achieved short-term photoreceptor protection in some rodent models of RP. Recombinant adeno-associated virus (rAAV) has shown promise in delivering therapeutic genes to photoreceptor cells. Consequently, a rAAV-CNTF vector was constructed that contains the CMV-driven murine CNTF cDNA linked to green fluorescent protein (GFP) through an IRES element. The IRE element allows for simultaneous expression of CNTF and GFP. The proposed research will determine: (1) the optimal dosage of rAAV-CNTF for maximal rescue of photoreceptors while causing minimal toxicity in the animal model of RP; (2) whether subretinal administration of rAAV-CNTF at early and later stage of degeneration will result in long-term rescue of photoreceptors in the rds/rds mouse, P23H an S344ter rhodopsin transgenic rats, as well as the rcd1 dog; (3) whether intravitreal administration of rAAV-CNTF at early and later stages of degeneration can lead to broader and long-term rescue of photoreceptors. The ability of CNTF to delay photoreceptor degeneration, regardless of recessive or dominant disease, may provide a general treatment for retinal degenerative diseases.